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Cell fate specification and differentiation in the adult mammalian intestine

Journal

NATURE REVIEWS MOLECULAR CELL BIOLOGY
Volume 22, Issue 1, Pages 39-53

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41580-020-0278-0

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Intestinal stem cells fuel tissue renewal, with the epithelium absorbing nutrients while acting as a barrier, lineage plasticity and niche signals enable efficient tissue repair, new insights from single-cell transcriptomics and organoid models reveal the importance of cell lineage plasticity and niche signals for tissue repair.
Intestinal stem cells at the bottom of crypts fuel the rapid renewal of the different cell types that constitute a multitasking tissue. The intestinal epithelium facilitates selective uptake of nutrients while acting as a barrier for hostile luminal contents. Recent discoveries have revealed that the lineage plasticity of committed cells - combined with redundant sources of niche signals - enables the epithelium to efficiently repair tissue damage. New approaches such as single-cell transcriptomics and the use of organoid models have led to the identification of the signals that guide fate specification of stem cell progeny into the six intestinal cell lineages. These cell types display context-dependent functionality and can adapt to different requirements over their lifetime, as dictated by their microenvironment. These new insights into stem cell regulation and fate specification could aid the development of therapies that exploit the regenerative capacity and functionality of the gut. The intestinal epithelium undergoes rapid turnover and is constantly exposed to hostile luminal contents. Recent insights from single-cell transcriptomics and organoid models have revealed that tissue repair is dependent on cell lineage plasticity and signals originating from different niche components.

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